Calcitriol Reduces Hepatic Triglyceride Accumulation and Glucose Output Through Ca2+/CaMKKβ/AMPK Activation Under Insulin-Resistant Conditions in Type 2 Diabetes Mellitus
| Autor: | D. Zhang, Q. Cheng, W. Y. So, S. Cheng, B. J. Boucher, Po Sing Leung |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Calcitriol medicine.medical_treatment Biochemistry 03 medical and health sciences Insulin resistance AMP-activated protein kinase Internal medicine polycyclic compounds medicine Protein kinase A Molecular Biology Calcium metabolism biology Chemistry Insulin AMPK Lipid metabolism General Medicine medicine.disease 030104 developmental biology Endocrinology biology.protein Molecular Medicine lipids (amino acids peptides and proteins) medicine.drug |
| Zdroj: | Current Molecular Medicine. 16:747-758 |
| ISSN: | 1566-5240 |
| DOI: | 10.2174/1566524016666160920111407 |
| Popis: | Objectives: The present study was designed to investigate the effects of calcitriol (the active hormonal metabolite of vitamin D) on hepatic metabolic abnormalities in type 2 diabetes. Methods: Type 2 diabetic db/db mice were used to investigate the effects of calcitriol on hepatic and systemic metabolic disorders. HepG2 cells cultured in insulin-resistant conditions were used to examine the potential mechanisms for calcitriol-induced changes in hepatic lipid and glucose metabolism. Results: 8-week calcitriol treatment ameliorated abnormal hepatic lipid and glucose production in db/db mice. In HepG2 cells under insulin-resistant condition, calcitriol increased cytosolic calcium concentration and induced 5’-AMP-activated protein kinase/acetyl-CoAcarboxylase (AMPK/ACC) phosphorylation via the Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ) pathway, contributing to the reductions in hepatic triglyceride accumulation and glucose output. Calcitriol also induced AMPK/ACC phosphorylation in liver of db/db mice. Conclusion: Our data indicate that calcitriol, at above-physiological serum concentrations, reduces hepatic triglyceride accumulation and glucose output, at least in part through activation of Ca2+/CaMKKβ/AMPK under insulin-resistant condition. |
| Databáze: | OpenAIRE |
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